Acute and Subacute Pulmonary Effects of Diesel Exhaust Particles in Mice: Pathological Changes and Translocation Pathways to the Circulation

Abstract

To study the acute and subacute pulmonary effects of diesel exhaust particles (DEPs), mice were intratracheally instilled with 25, 50 or 100 μg of DEPs for dose response experiments. Histological alterations were determined at 3 days post-exposure. 50 or 100 μg of DEPs produced mild to moderate pulmonary inflammation and tissue injury characterized by infiltration of neutrophils and active alveolar macrophages (AMs), focal alveolitis and particle-laden AMs accumulation. Ultrastructural studies of treated animals showed the dissociation of basement membranes and erosion of type I alveolar epithelial cells. To investigate the time response, mice were instilled with 50 μg of DEPs and sacrificed at intervals from 1 to 30 days post-exposure. DEPs induced pulmonary inflammation and injury at acute period; however, these changes gradually regressed during the experiment. These results suggest that instillation of small doses of DEPs causes transient acute mild to moderate lung inflammation and tissue damage. The evidences of the DEPs distribution in lung tissues were also elucidated throughout the observation time. The main possible translocation pathway of DEPs from the lung to the circulation in this study could be cell mediated active transportation and direct penetration through the area of alveolar interstitial damages.